Rana catesbeiana ribonuclease induces cell apoptosis via the caspase-9/-3 signaling pathway in human glioblastoma DBTRG, GBM8901 and GBM8401 cell lines

Abstract

Abstract. Human glioblastoma multiforme is one of the most aggressive malignant brain tumor types, and the mean survival time of patients with a brain tumor is <2 years when traditional therapies are administered. Thus, numerous studies have focused on the development of novel treatments for brain tumors. Frog ribonucleases, such as Onconase and Rana catesbeiana ribonuclease (RC-RNase), exert antitumor effects on various tumor cells, including cervical cancer, breast cancer, hepatoma, leukemia, pancreatic cancer and prostate cancer cells. In addition, frog Onconase has been applied as a treatment in clinical trials. However, the antitumor effects of frog ribonucleases on brain tumors are unclear. Previous studies have indicated that RC-RNase demonstrates a decreased cytotoxic effect in normal cells compared with Onconase. Therefore, the present study investigated the ability of RC-RNase to exert antitumor activities on human glioblastoma.It was found that RC-RNase inhibits the growth of the human glioblastoma DBTRG, GBM8901 and GBM8401 cells. In addition, the present study revealed that RC-RNase induces caspase-9/-3 activity and triggers the apoptotic cell death pathway in human glioblastoma cells. Notably, it was also demonstrated that RC-RNase effectively inhibits the growth of human glioblastoma tumors in a nude mouse model. Overall, the present study indicates that RC-RNase may be a potential agent for the treatment of human glioblastoma.

RNase activity of sialic acid-binding lectin from bullfrog eggs drives antitumor effect via the activation of p38 MAPK to caspase-3/7 signaling pathway in human breast cancer cells

“…Although SBL has been reported to activate caspase-3/7 ( 3 , 5 , 18 ), known as the major executioner caspases, the molecular mechanism remains unclear. Indeed, the caspase-3/7 activity in SBL-treated MDA-MB231 cells was 22-fold higher than that in the untreated cells ( Fig.…”

“…The internalization of SBL into cancer cells causes the degradation of ribosomal RNA, which leads to the inhibition of protein synthesis and, in turn, induces cell death ( 8 , 12 , 13 ). SBL-induced cell death is accompanied by mitochondrial dysfunction ( 14 ), endoplasmic reticulum stress ( 15 ), autophagocytosis ( 16 ), and caspase activation ( 3 , 5 ). Our previous studies showed that mitogen-activated protein kinases (MAPKs) were phosphorylated in two SBL-treated cell lines, human T-cell leukemia Jurkat cells and malignant mesothelioma NCI-H28 cells ( 14 , 17 ).…”

Sialic Acid-Binding Lectin from Bullfrog Eggs Exhibits an Anti-Tumor Effect Against Breast Cancer Cells Including Triple-Negative Phenotype Cells

“…It has been reported that cSBL acts as an anti-cancer agent against various human cancer cells including carcinoma (cervical, oral, hepatocellular, and breast), leukemia, lymphoma, mesothelioma, and glioblastoma [ 24 , 41 , 42 , 51 , 52 , 53 , 54 , 55 , 56 , 57 ]. Interestingly, although cSBL induces apoptosis in those cancer cells, normal tissue-derived cells, such as fibroblasts, melanocytes, keratinocytes, and mesothelial cells, are relatively insensitive to this agent [ 53 , 56 , 58 , 59 , 60 ].…”

Antitumor Potential of Marine and Freshwater Lectins

“…In other words, as Aristotle would suggest, in medio stat virtus. When inside the cell, SBLc activates the intrinsic apoptotic pathway on more than 30 tumor cell lines representing leukemia [107][108][109]118,120,131,132], Burkitt's lymphoma [108,109], cervical [133], hepatocellular [120,121,133], and estrogen-positive and -negative breast carcinomas [113,114,116,117,120], glioblastoma [119], and malignant mesothelioma [110,113] (Table 3).…”

“…For the record, pemetrexed, which is one of the drugs of choice currently used for the cure of mesothelioma, failed to eradicate murine MSTO-xenografted tumors on the same experimental conditions [113]. In addition, SBLc effectively inhibited the growth of glioblastoma tumors in nude mice once again without causing any side effect [119].…”